J Clin Periodontol 2013; 40: 1095–1103 doi: 10.1111/jcpe.12166
Systematic Review
Matrix metalloproteinase-1 promoter -1607 1G/2G polymorphism and chronic periodontitis susceptibility: a meta-analysis and systematic review
Wenyang Li1, Lin Xiao2 and Jing Hu1 1
State Key Laboratory of Oral Diseases and Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, China; 2 Department of Oral & Maxillofacial Surgery, Central Hospital of Fuling, Fuling, Chongqing, China
Li W, Xiao L, Hu J. Matrix metalloproteinase-1 promoter -1607 1G/2G polymorphism and chronic periodontitis susceptibility: a meta-analysis and systematic review. J Clin Periodontol 2013; 40: 1095–1103. doi: 10.1111/jcpe.12166.
Abstract Aim: Matrix metalloproteinase-1 promoter -1607 1G/2G (rs1799750) polymorphism have been shown to confer genetic susceptibility to chronic periodontitis (CP), but the results are inconsistent. Materials and Methods: A meta-analysis and systematic review was performed to accomplish a more precise estimation of the relationship. Results: Pooled estimates revealed that there was no significant association between this polymorphism and CP risk in Caucasian and Asian populations. In addition, it was reported by three Brazilian studies that no significant association was found for this polymorphism with CP risk in a Brazilian mixed population. Besides, there was no significant association of this polymorphism with mild to moderate and severe CP risk in both Caucasian and Asian populations. Moreover, both non-smokers and smokers did not have a significant association between this polymorphism and susceptibility to CP in Caucasian population. Conclusions: Matrix metalloproteinase-1 promoter 1607 1G/2G (rs1799750) polymorphism may have no effect on the disease susceptibility of CP in Caucasian, Asian and Brazilian mixed populations. Besides, this polymorphism may not play a direct role in severity of CP among both Caucasian and Asian populations, and between this polymorphism and smoking there may be no interactions to be associated with CP risk in Caucasian population.
Conflict of interest and source of funding statement This study was supported by National Nature Science Foundation of China (No. 81271106, 81321002). The authors declare that they have no conflict of interests.
Chronic periodontitis (CP), one of the most common form of periodontal disease, is highly prevalent and can affect up to 90% of the world’s population (Pihlstrom et al. 2005). CP is initiated by gram-negative bacteria, such as Porphyromonas
© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
Key words: chronic periodontitis; matrix metalloproteinase-1; meta-analysis; polymorphism Accepted for publication 1 September 2013
gingivalis, Treponema denticola and Tannerella forsythia (Feng & Weinberg 2006), and is characterized by inflammatory cell accumulation in the periodontal tissues, resulting in the destruction of periodontal attachment apparatus, including
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progressive attachment loss, bone resorption, pocket formation and gingival recession (Armitage 1999). During the destructive processes of CP, both environmental and genetic factors are involved and is influenced by interaction of periodontal pathogens and host responses (Offenbacher 1996). To date, a wide range of evidences have indicated that matrix metalloproteinases (MMPs) play an important role in the destructive processes of CP which is linked with the unbalanced production between MMPs and their endogenous tissue inhibitors (Kinane 2000). The MMPs represent a family of dependent metal ion endopeptidases and are classified according to their substrate specificity into collagenases, gelatinases, stromelysins and membranebound type (Birkedal-Hansen 1995). Currently, at least 28 kinds of MMPs have been reported, many of which have also been identified in inflamed periodontal tissues and gingival cervical fluid. These enzymes are thought to be crucial for the destructive processes of CP as they are capable of degrading all extracellular matrix components (Ingman et al. 1996). Matrix metalloproteinase-1 (MMP-1) or interstitial collagenase is the major type of proteolytic enzyme that can cleave native interstitial collagens types I and III, which are the most abundant protein components of periodontal extracellular matrix (Visse & Nagase 2003). In normal cells, physiologic levels of MMP-1 are low, but in pathological states, such as inflammation, there may be dysregulation of MMP-1 because the expression of MMP-1 is potently up-regulated by cytokines and growth factors (Vincenti et al. 1996). The MMP-1 gene is located in 11q22 (Pendas et al. 1996) and is translated in a wide variety of cells, such as fibroblasts, macrophages, endothelial and epithelial cells (BarOr et al. 2003). It is well known that gene expression can be influenced by a single nucleotide polymorphism located within the promoter and/or other regulatory regions of the gene. So polymorphisms of MMP-1 gene may have a functional consequence affecting the production or activity of MMP-1, and thus regulating the individual’s susceptibility to CP
(Pirhan et al. 2008, Repeke et al. 2009, Loo et al. 2011, Luczyszyn et al. 2012). Recently, one polymorphism in the promoter region of MMP-1 gene, -1607 1G/2G (rs1799750), has been well characterized (de Souza et al. 2003, Holla et al. 2004, Astolfi et al. 2006). Many studies have explored whether this polymorphism, which may differentially alter transcription activity and thus change the enzyme production, is associated with CP risk (Holla et al. 2004, Itagaki et al. 2004, Pirhan et al. 2008, Ustun et al. 2008). However, the observed associations of these studies are inconsistent and each of these trials has not been large enough to detect the effect of this polymorphism on CP risk. As a result, we performed a meta-analysis and systematic review of all eligible studies to derive more precise estimation of the association between this polymorphism and CP risk. The null hypothesis was that there was no significant association of this polymorphism with chronic periodontitis risk. Materials and Methods Protocols and eligibility criteria
The present meta-analysis and systematic review follows the Preferred Reporting Items for Systematic Review and Meta-analyses (PRISMA) statements (Appendix S1). And the focused question is adapted by using the Population, Intervention, Comparison, Outcomes (PICO) criteria. The literature search was limited to original studies performed in humans on the association of 1607 1G/2G polymorphism in the promoter region of MMP-1 gene with CP risk. There was no publication year restriction applied. Information sources and search strategy
An electronic search of the database PubMed (1966 to October 2012), Medline (1950 to October 2012) and Web of Science (1900 to October 2012) was carried out to identify relevant studies. Literature search keywords used in PubMed were ((((((((((“Matrix Metalloproteinase 1”[Mesh])) OR (Matrix Metalloproteinase 1)) OR (Matrix Metallopro-
teinase-1)) OR (interstitial collagenase)) OR (MMP 1)) OR (MMP1)) OR (MMP-1))) AND (((((“Polymorphism, Genetic”[Mesh])) OR (Polymorphism))) OR ((((“Genetic Variation”[Mesh])) OR (Genetic Variation)) OR (genetic variant)))) AND ((((((“Periodontitis”[Mesh])) OR (periodontitis))) OR (((((“Chronic Periodontitis”[Mesh])) OR (chronic periodontitis)) OR (CP)) OR (ChP))) OR ((((“Periodontal Diseases” [Mesh])) OR (periodontal disease)) OR (PD))). Other databases were searched with comparable terms, suitable for the specific database. Besides, the manual searching of reference lists from potentially relevant papers was also performed, based on the computer-assisted strategy, to identify any additional studies that may have been missed. Selection of studies
The inclusion criteria were: (a) studies used validated genotyping methods (for example, polymerase chain reaction–restriction fragment length polymorphism) to measure the association of 1607 1G/2G polymorphism in the promoter region of MMP-1 gene with CP risk; (b) studies in an appropriate analytical design (such as case control, cohort, or nested case control); (c) studies published in English; (d) studies with the available full-text and (e) data not duplicated in another manuscript. Studies were excluded if they did not report the relevant data to calculate the odds ratios and its variance. In addition, studies were also excluded if control subjects in these studies were varied from Hardy– Weinberg equilibrium (HWE). Data extraction
Using a pre-defined protocol, two reviewers (LWY and XL) independently performed the data extraction, with disagreements resolved through consensus decision. For each trial, the following items were collected: the surname of first author, year of publication, country, ethnicity [categorized as Caucasian, Asian or Mixed (the original study did not state the detailed ethnic result of subjects or mixed races)], sample size, severity of chronic periodontitis, matching criteria of cases
© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
MMP1-1607 SNP and CP risk: a meta-analysis and controls, genotyping methods, genes and variants genotyped as well as the evidence of HWE in controls through the application of online software (http://ihg2.helmholtz-muenchen.de/cgi-bin/hw/hwa1.pl). And a p–value less than 0.05 of HWE was considered significant. Risk of bias in individual studies
Two independent investigators (LWY and XL) evaluated the quality of the included studies according to a recently proposed specific quality assessment scale for periodontal genetic association studies (Nibali 2013). Briefly, the quality of each study was assessed by using the following methodological components: (a) selection; (b) comparability; (c) exposure; (d) study methodology/ design and (e) genetic analyses. The details of each methodological item are shown in Table 2. Scores ranged from 0 (lowest) to 20 (highest), and studies with scores ≥10 were classified as high-quality studies, whereas studies with scores
Systematic Review
Matrix metalloproteinase-1 promoter -1607 1G/2G polymorphism and chronic periodontitis susceptibility: a meta-analysis and systematic review
Wenyang Li1, Lin Xiao2 and Jing Hu1 1
State Key Laboratory of Oral Diseases and Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, China; 2 Department of Oral & Maxillofacial Surgery, Central Hospital of Fuling, Fuling, Chongqing, China
Li W, Xiao L, Hu J. Matrix metalloproteinase-1 promoter -1607 1G/2G polymorphism and chronic periodontitis susceptibility: a meta-analysis and systematic review. J Clin Periodontol 2013; 40: 1095–1103. doi: 10.1111/jcpe.12166.
Abstract Aim: Matrix metalloproteinase-1 promoter -1607 1G/2G (rs1799750) polymorphism have been shown to confer genetic susceptibility to chronic periodontitis (CP), but the results are inconsistent. Materials and Methods: A meta-analysis and systematic review was performed to accomplish a more precise estimation of the relationship. Results: Pooled estimates revealed that there was no significant association between this polymorphism and CP risk in Caucasian and Asian populations. In addition, it was reported by three Brazilian studies that no significant association was found for this polymorphism with CP risk in a Brazilian mixed population. Besides, there was no significant association of this polymorphism with mild to moderate and severe CP risk in both Caucasian and Asian populations. Moreover, both non-smokers and smokers did not have a significant association between this polymorphism and susceptibility to CP in Caucasian population. Conclusions: Matrix metalloproteinase-1 promoter 1607 1G/2G (rs1799750) polymorphism may have no effect on the disease susceptibility of CP in Caucasian, Asian and Brazilian mixed populations. Besides, this polymorphism may not play a direct role in severity of CP among both Caucasian and Asian populations, and between this polymorphism and smoking there may be no interactions to be associated with CP risk in Caucasian population.
Conflict of interest and source of funding statement This study was supported by National Nature Science Foundation of China (No. 81271106, 81321002). The authors declare that they have no conflict of interests.
Chronic periodontitis (CP), one of the most common form of periodontal disease, is highly prevalent and can affect up to 90% of the world’s population (Pihlstrom et al. 2005). CP is initiated by gram-negative bacteria, such as Porphyromonas
© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
Key words: chronic periodontitis; matrix metalloproteinase-1; meta-analysis; polymorphism Accepted for publication 1 September 2013
gingivalis, Treponema denticola and Tannerella forsythia (Feng & Weinberg 2006), and is characterized by inflammatory cell accumulation in the periodontal tissues, resulting in the destruction of periodontal attachment apparatus, including
1095
1096
Li et al.
progressive attachment loss, bone resorption, pocket formation and gingival recession (Armitage 1999). During the destructive processes of CP, both environmental and genetic factors are involved and is influenced by interaction of periodontal pathogens and host responses (Offenbacher 1996). To date, a wide range of evidences have indicated that matrix metalloproteinases (MMPs) play an important role in the destructive processes of CP which is linked with the unbalanced production between MMPs and their endogenous tissue inhibitors (Kinane 2000). The MMPs represent a family of dependent metal ion endopeptidases and are classified according to their substrate specificity into collagenases, gelatinases, stromelysins and membranebound type (Birkedal-Hansen 1995). Currently, at least 28 kinds of MMPs have been reported, many of which have also been identified in inflamed periodontal tissues and gingival cervical fluid. These enzymes are thought to be crucial for the destructive processes of CP as they are capable of degrading all extracellular matrix components (Ingman et al. 1996). Matrix metalloproteinase-1 (MMP-1) or interstitial collagenase is the major type of proteolytic enzyme that can cleave native interstitial collagens types I and III, which are the most abundant protein components of periodontal extracellular matrix (Visse & Nagase 2003). In normal cells, physiologic levels of MMP-1 are low, but in pathological states, such as inflammation, there may be dysregulation of MMP-1 because the expression of MMP-1 is potently up-regulated by cytokines and growth factors (Vincenti et al. 1996). The MMP-1 gene is located in 11q22 (Pendas et al. 1996) and is translated in a wide variety of cells, such as fibroblasts, macrophages, endothelial and epithelial cells (BarOr et al. 2003). It is well known that gene expression can be influenced by a single nucleotide polymorphism located within the promoter and/or other regulatory regions of the gene. So polymorphisms of MMP-1 gene may have a functional consequence affecting the production or activity of MMP-1, and thus regulating the individual’s susceptibility to CP
(Pirhan et al. 2008, Repeke et al. 2009, Loo et al. 2011, Luczyszyn et al. 2012). Recently, one polymorphism in the promoter region of MMP-1 gene, -1607 1G/2G (rs1799750), has been well characterized (de Souza et al. 2003, Holla et al. 2004, Astolfi et al. 2006). Many studies have explored whether this polymorphism, which may differentially alter transcription activity and thus change the enzyme production, is associated with CP risk (Holla et al. 2004, Itagaki et al. 2004, Pirhan et al. 2008, Ustun et al. 2008). However, the observed associations of these studies are inconsistent and each of these trials has not been large enough to detect the effect of this polymorphism on CP risk. As a result, we performed a meta-analysis and systematic review of all eligible studies to derive more precise estimation of the association between this polymorphism and CP risk. The null hypothesis was that there was no significant association of this polymorphism with chronic periodontitis risk. Materials and Methods Protocols and eligibility criteria
The present meta-analysis and systematic review follows the Preferred Reporting Items for Systematic Review and Meta-analyses (PRISMA) statements (Appendix S1). And the focused question is adapted by using the Population, Intervention, Comparison, Outcomes (PICO) criteria. The literature search was limited to original studies performed in humans on the association of 1607 1G/2G polymorphism in the promoter region of MMP-1 gene with CP risk. There was no publication year restriction applied. Information sources and search strategy
An electronic search of the database PubMed (1966 to October 2012), Medline (1950 to October 2012) and Web of Science (1900 to October 2012) was carried out to identify relevant studies. Literature search keywords used in PubMed were ((((((((((“Matrix Metalloproteinase 1”[Mesh])) OR (Matrix Metalloproteinase 1)) OR (Matrix Metallopro-
teinase-1)) OR (interstitial collagenase)) OR (MMP 1)) OR (MMP1)) OR (MMP-1))) AND (((((“Polymorphism, Genetic”[Mesh])) OR (Polymorphism))) OR ((((“Genetic Variation”[Mesh])) OR (Genetic Variation)) OR (genetic variant)))) AND ((((((“Periodontitis”[Mesh])) OR (periodontitis))) OR (((((“Chronic Periodontitis”[Mesh])) OR (chronic periodontitis)) OR (CP)) OR (ChP))) OR ((((“Periodontal Diseases” [Mesh])) OR (periodontal disease)) OR (PD))). Other databases were searched with comparable terms, suitable for the specific database. Besides, the manual searching of reference lists from potentially relevant papers was also performed, based on the computer-assisted strategy, to identify any additional studies that may have been missed. Selection of studies
The inclusion criteria were: (a) studies used validated genotyping methods (for example, polymerase chain reaction–restriction fragment length polymorphism) to measure the association of 1607 1G/2G polymorphism in the promoter region of MMP-1 gene with CP risk; (b) studies in an appropriate analytical design (such as case control, cohort, or nested case control); (c) studies published in English; (d) studies with the available full-text and (e) data not duplicated in another manuscript. Studies were excluded if they did not report the relevant data to calculate the odds ratios and its variance. In addition, studies were also excluded if control subjects in these studies were varied from Hardy– Weinberg equilibrium (HWE). Data extraction
Using a pre-defined protocol, two reviewers (LWY and XL) independently performed the data extraction, with disagreements resolved through consensus decision. For each trial, the following items were collected: the surname of first author, year of publication, country, ethnicity [categorized as Caucasian, Asian or Mixed (the original study did not state the detailed ethnic result of subjects or mixed races)], sample size, severity of chronic periodontitis, matching criteria of cases
© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
MMP1-1607 SNP and CP risk: a meta-analysis and controls, genotyping methods, genes and variants genotyped as well as the evidence of HWE in controls through the application of online software (http://ihg2.helmholtz-muenchen.de/cgi-bin/hw/hwa1.pl). And a p–value less than 0.05 of HWE was considered significant. Risk of bias in individual studies
Two independent investigators (LWY and XL) evaluated the quality of the included studies according to a recently proposed specific quality assessment scale for periodontal genetic association studies (Nibali 2013). Briefly, the quality of each study was assessed by using the following methodological components: (a) selection; (b) comparability; (c) exposure; (d) study methodology/ design and (e) genetic analyses. The details of each methodological item are shown in Table 2. Scores ranged from 0 (lowest) to 20 (highest), and studies with scores ≥10 were classified as high-quality studies, whereas studies with scores
